Content developed by Marie Fuzzati (IRCCS Mondino Foundation and France Parkinson) and Ludivine Breger (INSERM), in close collaboration with MIUR. For more information or for questions, please contact experimentalmodels@jpnd.eu.

Transgene expression

6 months: Protein expression is about 6 fold higher than that of the endogenous LRRK2 in the striatum of transgenic animals.

Neurodegeneration

Up to 18 months: No differences is observed in the number of TH-positive cells in the SN or in the density of TH fibres measured in the striatum.

Dopamine Homeostasis

6 and 12 months: No differences in the level of DA and HVA are observed in the striatum of these animals (compared to control mice).

10 months: no differences are observed in striatal TH protein levels, enzymatic activity, or phosphorylation state when compared to control mice. Similarly VMAT2, DAT, or D2 receptor levels are comparable to wild type animals.

Inclusions

Up to 18 months: No alpha-synuclein and/or ubiquitin inclusions are visible.

Motor Behaviours

6 and 12 months: The overall activity of the animals is increased: more rearing events (at both time points), longer distances travelled and longer periods of activity (only at 12 months) in the open field than the littermate control mice or LRRK2G2019S transgenic animals (add link to page). The animals also make more mistakes on the challenge beam (slips and slips/step) than the control or LRRK2G2019S transgenic mice.

Response to dopaminergic treatment

Not reported

Non-motor Behaviours

Not reported

Electrophysiology

12 months: An increase in electrical stimulation-evoked DA release is observed in LRRK2 transgenic animals compared to paired littermate control mice (fast-scan cyclic voltammetry). However, the maximum uptake rate of DA is not altered.

Neuroinflammation

Not reported

The EU Joint Programme – Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases, in particular Alzheimer’s. Learn More